Cytomegalovirus (CMV) has been implicated in the pathogenesis of atherosclerosis, but data suggest there is considerable variability in host susceptibility. The cellular immune response is crucial in host defense against intracellular pathogens. We tested the concept that different individuals have different cellular immune responses to CMV by measuring, in 4 healthy blood donors, the IFNgamma response of CD8 T lymphocytes to CMV antigens(Ag). CD8 T cells were isolated from peripheral blood cells and exposed to CMV infected HEL299 cells 3X at weekly intervals. These stimulated CD8 T cells responded to CMV Ag by releasing IFNg in the supernatant (Fig 1); specificity was demonstrated by the fact that considerably less IFNgamma was released in response to Flu peptide. Negligible amounts of IFNg were produced by CD8cells stimulated by non infected HEL299 cells(control). Biologic activity of the CD8 response to CMV Ag was demonstrated by the finding that treatment of CMV-infected HEL299 cells with supernatant containing IFNgamma inhibited replication of CMV. Importantly, we found a quantitative variation in the IFNgamma response among the 4 individuals. Local release of IFNgamma can, through multiple mechanisms, modulate both host response to pathogen and pathogen activity. Our results, by demonstrating individual variability in the immune response to CMV infection, are therefore compatible with the concept that individuals will also vary in their susceptibility or resistance to CMV-mediated contribution to atherosclerosis.